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Published in: Clinical and Translational Oncology 7/2017

01-07-2017 | Review Article

Retroperitoneal lymph node dissection: an update in testicular malignancies

Author: K. Yadav

Published in: Clinical and Translational Oncology | Issue 7/2017

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Abstract

Management of testicular cancer has evolved through many breakthroughs. The decades of zeal to improve oncologic adequacy and to decrease morbidity has led to the current scientific knowledge of retroperitoneal lymph node dissection templates. Retroperitoneal lymph node dissection (RPLND) has potential for staging, prognostication and therapeutic importance in the management of testicular malignancy. RPLND has overcome limitations of current imaging which understage 30% of stage I disease and overstage 25–30% of stage II disease. For low-volume disease, RPLND is curative in up to 90% cases without adjuvant therapy and has important role in postchemotherapy residual disease. Risk of recurrence after RPLND is 1% and follow-up imaging can be limited, thus avoiding their potential risk of radiation exposure. RPLND reveals vital information of disease nature and guide adjuvant therapy. Despite the long evolution period, certain controversies still surround RPLND. We aim to refine this challenging management in the following manuscript based on available evidence.
Literature
1.
go back to reference Skandalakis JE. Surgical anatomy: the embryologic and anatomic basis of modern surgery. Male genital system. chapter 25. New York: McGraw Hill; 2004. Skandalakis JE. Surgical anatomy: the embryologic and anatomic basis of modern surgery. Male genital system. chapter 25. New York: McGraw Hill; 2004.
2.
go back to reference Most A. Uber die lymphgefässe und lymphdrüssendes hodens. Arch f Anat u Entweckingsgesh. 1899;113:387–93 (in German). Most A. Uber die lymphgefässe und lymphdrüssendes hodens. Arch f Anat u Entweckingsgesh. 1899;113:387–93 (in German).
3.
go back to reference Jamieson JK, Dobson JF. On the injection of lymphatics by prussian blue. J AnatPhysiol. 1910;45(Pt 1):7–10. Jamieson JK, Dobson JF. On the injection of lymphatics by prussian blue. J AnatPhysiol. 1910;45(Pt 1):7–10.
4.
go back to reference Cuneo B. Note sur les lymphatiques du testicule. Bull Mem Soc Anat Paris. 1901;76:105 (in French). Cuneo B. Note sur les lymphatiques du testicule. Bull Mem Soc Anat Paris. 1901;76:105 (in French).
5.
go back to reference Chevassu M. Deuxcasd’epitheliome du testiculetraite par castration et l’ablation des ganglions lumboaortique. Bull MemSoc Chir Paris. 1910;36:236–62 (in French). Chevassu M. Deuxcasd’epitheliome du testiculetraite par castration et l’ablation des ganglions lumboaortique. Bull MemSoc Chir Paris. 1910;36:236–62 (in French).
6.
go back to reference Bland-Sutton J. An operation for lumbar gland removal in cases of testis tumour. Lancet. 1909;1:1406. Bland-Sutton J. An operation for lumbar gland removal in cases of testis tumour. Lancet. 1909;1:1406.
7.
go back to reference Hinman F. The operative treatment of tumors of the testicle. JAMA. 1914;58:2009–15.CrossRef Hinman F. The operative treatment of tumors of the testicle. JAMA. 1914;58:2009–15.CrossRef
8.
go back to reference Patton JF, Hewitt CB, Mallis N. Diagnosis and treatment of tumors of the testis. J Am Med Assoc. 1959;171:2194–8.CrossRefPubMed Patton JF, Hewitt CB, Mallis N. Diagnosis and treatment of tumors of the testis. J Am Med Assoc. 1959;171:2194–8.CrossRefPubMed
9.
go back to reference Cooper J, Leadbetter W, Chute R. The thoracoabdominal approach for retroperitoneal gland dissection: its application to testis tumors. Surg Gynecol Obstet. 1950;90:486. Cooper J, Leadbetter W, Chute R. The thoracoabdominal approach for retroperitoneal gland dissection: its application to testis tumors. Surg Gynecol Obstet. 1950;90:486.
10.
go back to reference Donohue JP. Retroperitoneal lymphadenectomy: the anterior approach including bilateral suprarenal-hilar dissection. Urol Clin North Am. 1977;4(3):509–21.PubMed Donohue JP. Retroperitoneal lymphadenectomy: the anterior approach including bilateral suprarenal-hilar dissection. Urol Clin North Am. 1977;4(3):509–21.PubMed
11.
go back to reference Busch FM, Sayegh ES. Roentgenographic visualization of human testicular lymphatics: a preliminary report. J Urol. 1963;89:106–10.PubMed Busch FM, Sayegh ES. Roentgenographic visualization of human testicular lymphatics: a preliminary report. J Urol. 1963;89:106–10.PubMed
12.
go back to reference Ray B, Hajdu SI, Whitmore WF Jr. Proceedings: distribution of retroperitoneal lymph node metastases in testicular germinal tumors. Cancer. 1974;33(2):340–8.CrossRefPubMed Ray B, Hajdu SI, Whitmore WF Jr. Proceedings: distribution of retroperitoneal lymph node metastases in testicular germinal tumors. Cancer. 1974;33(2):340–8.CrossRefPubMed
13.
go back to reference Weisbach L, Boedefeld E. Localization of solitary and multiple metastasis in stage II non seminomatous testis tumors as a basis for a modified staging lymph node dissection in stage I. J Urol. 1982;138:77–82. Weisbach L, Boedefeld E. Localization of solitary and multiple metastasis in stage II non seminomatous testis tumors as a basis for a modified staging lymph node dissection in stage I. J Urol. 1982;138:77–82.
14.
go back to reference Donohue J, Zachary J, Maynard S. Distribution of nodal metastases in non-seminomatous testicular cancer. J Urol. 1982;128:315–20.PubMed Donohue J, Zachary J, Maynard S. Distribution of nodal metastases in non-seminomatous testicular cancer. J Urol. 1982;128:315–20.PubMed
15.
go back to reference Narayan P, Lange P, Fraley E. Ejaculation and fertility after extended retro-peritoneal lymph node dissection for testicular cancer. World J Urol. 1982;127:685. Narayan P, Lange P, Fraley E. Ejaculation and fertility after extended retro-peritoneal lymph node dissection for testicular cancer. World J Urol. 1982;127:685.
16.
go back to reference Jewett M, Kong Y, Goldberg J. Retroperitoneal lymphadenectomy for testicular tumor with preservation of ejaculation. J Urol. 1988;139:1220–4.PubMed Jewett M, Kong Y, Goldberg J. Retroperitoneal lymphadenectomy for testicular tumor with preservation of ejaculation. J Urol. 1988;139:1220–4.PubMed
17.
go back to reference Donohue JP, Thornhill JA, Foster RS. Retroperitoneal lymphadenectomy for clinical stage a testis cancer (1965 to 1989): modifications of technique and impact on ejaculation. J Urol. 1993;149(2):237–43.PubMed Donohue JP, Thornhill JA, Foster RS. Retroperitoneal lymphadenectomy for clinical stage a testis cancer (1965 to 1989): modifications of technique and impact on ejaculation. J Urol. 1993;149(2):237–43.PubMed
18.
go back to reference Sogani PC. Evolution of the management of stage I nonseminomatous germ-cell tumors of the testis. Urol Clin North Am. 1991;18(3):561–73.PubMed Sogani PC. Evolution of the management of stage I nonseminomatous germ-cell tumors of the testis. Urol Clin North Am. 1991;18(3):561–73.PubMed
19.
go back to reference Brydoy M, Fossa SD, Klepp O. Paternity following treatment for testicular cancer. J Natl Cancer Inst. 2005;97:1580.CrossRefPubMed Brydoy M, Fossa SD, Klepp O. Paternity following treatment for testicular cancer. J Natl Cancer Inst. 2005;97:1580.CrossRefPubMed
20.
go back to reference Lange PH, Narayan P, Fraley EE. Fertility issues following therapy for testicular cancer. Semin Ural. 1984;2(4):264–74. Lange PH, Narayan P, Fraley EE. Fertility issues following therapy for testicular cancer. Semin Ural. 1984;2(4):264–74.
21.
go back to reference Sheinfeld J. Nonseminomatous germ cell tumors of the testis: current concepts and controversies. Urology. 1994;44(1):2–14.CrossRefPubMed Sheinfeld J. Nonseminomatous germ cell tumors of the testis: current concepts and controversies. Urology. 1994;44(1):2–14.CrossRefPubMed
22.
go back to reference Narayan P, Lange PH, Fraley EE. Ejaculation and fertility after extended retroperitoneal lymph node dissection for testicular cancer. J Urol. 1982;127(4):685–8.PubMed Narayan P, Lange PH, Fraley EE. Ejaculation and fertility after extended retroperitoneal lymph node dissection for testicular cancer. J Urol. 1982;127(4):685–8.PubMed
23.
go back to reference Richie JP. Clinical stage 1 testicular cancer: the role of modified retroperitoneal lymphadenectomy. J Urol. 1990;144(5):1160–3.PubMed Richie JP. Clinical stage 1 testicular cancer: the role of modified retroperitoneal lymphadenectomy. J Urol. 1990;144(5):1160–3.PubMed
24.
go back to reference Fossa SD, Klepp O, Ous S. Unilateral retroperitoneal lymph node dissection in patients with nonseminomatous testicular tumor in clinical stage I. Eur Urol. 1984;10(1):17–23.PubMed Fossa SD, Klepp O, Ous S. Unilateral retroperitoneal lymph node dissection in patients with nonseminomatous testicular tumor in clinical stage I. Eur Urol. 1984;10(1):17–23.PubMed
25.
go back to reference Jewett MA, Kong YS, Goldberg SD. Retroperitoneal lymphadenectomy for testis tumor with nerve sparing for ejaculation. J Urol. 1988;139(6):1220–4.PubMed Jewett MA, Kong YS, Goldberg SD. Retroperitoneal lymphadenectomy for testis tumor with nerve sparing for ejaculation. J Urol. 1988;139(6):1220–4.PubMed
26.
go back to reference Donohue JP, Foster RS, Rowland RG. Nerve sparing retroperitoneal lymphadenectomy with preservation of ejaculation. J Urol. 1990;144(2 Pt 1):287–92.PubMed Donohue JP, Foster RS, Rowland RG. Nerve sparing retroperitoneal lymphadenectomy with preservation of ejaculation. J Urol. 1990;144(2 Pt 1):287–92.PubMed
27.
go back to reference Murphy BR, Breeden ES, Donohue JP. Surgical salvage of chemorefractory germ cell tumors. J Clin Oncol. 1993;11:324.CrossRefPubMed Murphy BR, Breeden ES, Donohue JP. Surgical salvage of chemorefractory germ cell tumors. J Clin Oncol. 1993;11:324.CrossRefPubMed
28.
go back to reference Ong Teng A, Winkler Mathias H, Savage Philip M, Seckl Michael J, Christmas Timothy J. Retroperitoneal lymph node dissection after chemotherapy in patients with elevated tumour markers: indications, histopathology and outcome. BJUI. 2008;2:198–202.CrossRef Ong Teng A, Winkler Mathias H, Savage Philip M, Seckl Michael J, Christmas Timothy J. Retroperitoneal lymph node dissection after chemotherapy in patients with elevated tumour markers: indications, histopathology and outcome. BJUI. 2008;2:198–202.CrossRef
29.
go back to reference Wood DP Jr, Herr HW, Motzer RJ. Surgical resection of solitary metastases after chemotherapy in patients with nonseminomatous germ cell tumors and elevated serum tumor markers. Cancer. 1992;70:2354.CrossRefPubMed Wood DP Jr, Herr HW, Motzer RJ. Surgical resection of solitary metastases after chemotherapy in patients with nonseminomatous germ cell tumors and elevated serum tumor markers. Cancer. 1992;70:2354.CrossRefPubMed
30.
go back to reference Heidenreich A, Sesterhenn IA, Mostofi FK, Moul JW. Prognostic risk factors that identify patients with clinical stage I nonseminomatous germ cell tumors at low risk and high risk for metastasis. Cancer. 1998;83:1002.CrossRefPubMed Heidenreich A, Sesterhenn IA, Mostofi FK, Moul JW. Prognostic risk factors that identify patients with clinical stage I nonseminomatous germ cell tumors at low risk and high risk for metastasis. Cancer. 1998;83:1002.CrossRefPubMed
31.
go back to reference Choueiri TK, Stephenson AJ, Gilligan T, et al. Management of clinical stage I nonseminomatous germ cell testicular cancer. Urol Clin North Am. 2007;34(2):137–48 (abstract: viii).CrossRefPubMed Choueiri TK, Stephenson AJ, Gilligan T, et al. Management of clinical stage I nonseminomatous germ cell testicular cancer. Urol Clin North Am. 2007;34(2):137–48 (abstract: viii).CrossRefPubMed
32.
go back to reference Tarin TV, Sonn G, Shinghal R. Estimating the risk of cancer associated with imaging related radiation during surveillance for stage I testicular cancer using computerized tomography. J Urol. 2009;181(2):627–32.CrossRefPubMed Tarin TV, Sonn G, Shinghal R. Estimating the risk of cancer associated with imaging related radiation during surveillance for stage I testicular cancer using computerized tomography. J Urol. 2009;181(2):627–32.CrossRefPubMed
33.
go back to reference Chamie K, Kurzrock EA, Evans CP. Secondary malignancies among nonseminomatous germ cell tumor cancer survivors. Cancer. 2011;117(18):v4219–30.CrossRef Chamie K, Kurzrock EA, Evans CP. Secondary malignancies among nonseminomatous germ cell tumor cancer survivors. Cancer. 2011;117(18):v4219–30.CrossRef
34.
go back to reference Stephenson AJ, Sheinfeld J. The role of retroperitoneal lymph node dissection in the management of testicular cancer. Urol Oncol. 2004;22(3):225–33.CrossRefPubMed Stephenson AJ, Sheinfeld J. The role of retroperitoneal lymph node dissection in the management of testicular cancer. Urol Oncol. 2004;22(3):225–33.CrossRefPubMed
35.
go back to reference Stephenson Andrew J, Bosl George J, Motzer Robert J, Kattan Michael W, Stasi Jason, Bajorin Dean F, Sheinfeld Joel. Retroperitoneal lymph node dissection for nonseminomatous germ cell testicular cancer: impact of patient selection factors on outcome. J Clin Oncol. 2005;23(12):2781–8.CrossRefPubMed Stephenson Andrew J, Bosl George J, Motzer Robert J, Kattan Michael W, Stasi Jason, Bajorin Dean F, Sheinfeld Joel. Retroperitoneal lymph node dissection for nonseminomatous germ cell testicular cancer: impact of patient selection factors on outcome. J Clin Oncol. 2005;23(12):2781–8.CrossRefPubMed
36.
go back to reference George DW, Foster RS, Hromas RA, et al. Update on late relapse of germ cell tumor: a clinical and molecular analysis. J Clin Oncol. 2003;21(1):113–22.CrossRefPubMed George DW, Foster RS, Hromas RA, et al. Update on late relapse of germ cell tumor: a clinical and molecular analysis. J Clin Oncol. 2003;21(1):113–22.CrossRefPubMed
37.
go back to reference de Bruin MJ, Oosterhof GO, Debruyne FM. Nerve-sparing retroperitoneal lymphadenectomy for low stage testicular cancer. Br J Urol. 1993;71(3):336–9.CrossRefPubMed de Bruin MJ, Oosterhof GO, Debruyne FM. Nerve-sparing retroperitoneal lymphadenectomy for low stage testicular cancer. Br J Urol. 1993;71(3):336–9.CrossRefPubMed
38.
go back to reference Stephenson Andrew J, Bosl George J, Motzer Robert J, Bajorin Dean F, Stasi Jason P, Seinfeld Joel. Nonrandomized comparison of primary chemotherapy and retroperitoneal lymph node dissection for clinical stage IIa and IIb nonseminomatous germ cell testicular cancer. J Clin Oncol. 2007;25(35):5597–602.CrossRefPubMed Stephenson Andrew J, Bosl George J, Motzer Robert J, Bajorin Dean F, Stasi Jason P, Seinfeld Joel. Nonrandomized comparison of primary chemotherapy and retroperitoneal lymph node dissection for clinical stage IIa and IIb nonseminomatous germ cell testicular cancer. J Clin Oncol. 2007;25(35):5597–602.CrossRefPubMed
39.
go back to reference Hartmann JT, Schmoll H-J, Kuczyk MA, Candelaria M, Bokemeyer C. Postchemotherapy resections of residual masses from metastatic non-seminomatous testicular germ cell tumours. Ann Oncol. 1997;8(6):531–8.CrossRefPubMed Hartmann JT, Schmoll H-J, Kuczyk MA, Candelaria M, Bokemeyer C. Postchemotherapy resections of residual masses from metastatic non-seminomatous testicular germ cell tumours. Ann Oncol. 1997;8(6):531–8.CrossRefPubMed
40.
go back to reference Sheinfeld JB, Bartsch G, Bosl G. Surgery for testicular tumors. In: Wein AJ, editor. Campbell-walshurology. 9th ed. Philadelphia: Saunders Elsevier; 2007. p. 936–64. Sheinfeld JB, Bartsch G, Bosl G. Surgery for testicular tumors. In: Wein AJ, editor. Campbell-walshurology. 9th ed. Philadelphia: Saunders Elsevier; 2007. p. 936–64.
41.
go back to reference Logothetis CJ, Samuels ML, Trindade A. The growing teratoma syndrome. Cancer. 1982;50(8):1629–35.CrossRefPubMed Logothetis CJ, Samuels ML, Trindade A. The growing teratoma syndrome. Cancer. 1982;50(8):1629–35.CrossRefPubMed
42.
go back to reference Motzer RJ, Amsterdam A, Prieto V. Teratoma with malignant transformation: diverse malignant histologies arising in men with germ cell tumors. J Urol. 1998;159(1):133–8.CrossRefPubMed Motzer RJ, Amsterdam A, Prieto V. Teratoma with malignant transformation: diverse malignant histologies arising in men with germ cell tumors. J Urol. 1998;159(1):133–8.CrossRefPubMed
43.
go back to reference Baniel J, Foster RS, Gonin R. Late relapse of testicular cancer. J Clin Oncol. 1995;13(5):1170–6.CrossRefPubMed Baniel J, Foster RS, Gonin R. Late relapse of testicular cancer. J Clin Oncol. 1995;13(5):1170–6.CrossRefPubMed
44.
go back to reference De Santis M, Becherer A, Bokemeyer C, Stoiber F, Oechsle K, Sellner F, Lang A, et al. 2-18fluoro-deoxy-d-glucose positron emission tomography is a reliable predictor for viable tumor in postchemotherapy seminoma: an update of the prospective multicentric SEMPET trial. J Clin Oncol. 2004;22(6):1034–9.CrossRefPubMed De Santis M, Becherer A, Bokemeyer C, Stoiber F, Oechsle K, Sellner F, Lang A, et al. 2-18fluoro-deoxy-d-glucose positron emission tomography is a reliable predictor for viable tumor in postchemotherapy seminoma: an update of the prospective multicentric SEMPET trial. J Clin Oncol. 2004;22(6):1034–9.CrossRefPubMed
45.
go back to reference Steyerberg EW, Keizer HJ, Fossa SD. Prediction of residual retroperitoneal mass histology after chemotherapy for metastatic non seminomatous germ cell tumor: multivariate analysis of individual patient data from six study groups. J Clin Oncol. 1995;13(5):1177–87.CrossRefPubMed Steyerberg EW, Keizer HJ, Fossa SD. Prediction of residual retroperitoneal mass histology after chemotherapy for metastatic non seminomatous germ cell tumor: multivariate analysis of individual patient data from six study groups. J Clin Oncol. 1995;13(5):1177–87.CrossRefPubMed
46.
go back to reference Ehrlich Y, Brames M, Beck S. Long-term followup of cisplatin combination chemotherapy in patients with disseminated nonseminomatous germ cell tumors: is a post-chemotherapy retroperitoneal lymph node dissection needed after complete remission? J Clin Oncol. 2010;28(4):531–6.CrossRefPubMed Ehrlich Y, Brames M, Beck S. Long-term followup of cisplatin combination chemotherapy in patients with disseminated nonseminomatous germ cell tumors: is a post-chemotherapy retroperitoneal lymph node dissection needed after complete remission? J Clin Oncol. 2010;28(4):531–6.CrossRefPubMed
47.
go back to reference Oldenburg J, Alfsen GC, Lien HH, Aass N, Waehre H. Fossa SD Postchemotherapy retroperitoneal surgery remains necessary in patients with nonseminomatous testicular cancer and minimal residual tumor masses. J Clin Oncol. 2003;21(17):3310–7.CrossRefPubMed Oldenburg J, Alfsen GC, Lien HH, Aass N, Waehre H. Fossa SD Postchemotherapy retroperitoneal surgery remains necessary in patients with nonseminomatous testicular cancer and minimal residual tumor masses. J Clin Oncol. 2003;21(17):3310–7.CrossRefPubMed
48.
go back to reference Bosl GJ, Motzer RJ. Weighing risks and benefits of postchemotherapy retroperitoneal lymph node dissection: not so easy. JCO. 2010;28(4):519–21.CrossRef Bosl GJ, Motzer RJ. Weighing risks and benefits of postchemotherapy retroperitoneal lymph node dissection: not so easy. JCO. 2010;28(4):519–21.CrossRef
49.
go back to reference Weissbach L, Boedefeld EA, Horstmann-Dubral B. Surgical treatment of stage-I non-seminomatous germ cell testis tumor. Final results of a prospective multicenter trial 1982–1987. Testicular Tumor Study Group. Eur Urol. 1990;17(2):97–106.PubMed Weissbach L, Boedefeld EA, Horstmann-Dubral B. Surgical treatment of stage-I non-seminomatous germ cell testis tumor. Final results of a prospective multicenter trial 1982–1987. Testicular Tumor Study Group. Eur Urol. 1990;17(2):97–106.PubMed
50.
go back to reference Eggener SE, Carver BS, Sharp DS. Incidence of disease outside modified retroperitoneal lymph node dissection templates in clinical stage I or IIA nonseminomatous germ cell testicular cancer. J Urol. 2007;177(3):937–42.CrossRefPubMed Eggener SE, Carver BS, Sharp DS. Incidence of disease outside modified retroperitoneal lymph node dissection templates in clinical stage I or IIA nonseminomatous germ cell testicular cancer. J Urol. 2007;177(3):937–42.CrossRefPubMed
51.
go back to reference Carver BS, Shayegan B, Eggener S. Incidence of metastatic nonseminomatous germ cell tumor outside the boundaries of a modified postchemotherapy retroperitoneal lymph node dissection. J Clin Oncol. 2007;25(28):4365–9.CrossRefPubMed Carver BS, Shayegan B, Eggener S. Incidence of metastatic nonseminomatous germ cell tumor outside the boundaries of a modified postchemotherapy retroperitoneal lymph node dissection. J Clin Oncol. 2007;25(28):4365–9.CrossRefPubMed
52.
53.
go back to reference Carver B, Cronin A, Eggener S. The total number of retroperitoneal lymph nodes resected impacts clinical outcome after chemotherapy for metastatic testicular cancer. Urology. 2010;75(6):1431–5.CrossRefPubMedPubMedCentral Carver B, Cronin A, Eggener S. The total number of retroperitoneal lymph nodes resected impacts clinical outcome after chemotherapy for metastatic testicular cancer. Urology. 2010;75(6):1431–5.CrossRefPubMedPubMedCentral
54.
go back to reference Steiner H, Zangerl F, Sthr B. Results of bilateral nerve sparing laparoscopic retroperitoneal lymph node dissection for testicular cancer. J Urol. 2008;180(4):1348–52.CrossRefPubMed Steiner H, Zangerl F, Sthr B. Results of bilateral nerve sparing laparoscopic retroperitoneal lymph node dissection for testicular cancer. J Urol. 2008;180(4):1348–52.CrossRefPubMed
Metadata
Title
Retroperitoneal lymph node dissection: an update in testicular malignancies
Author
K. Yadav
Publication date
01-07-2017
Publisher
Springer International Publishing
Published in
Clinical and Translational Oncology / Issue 7/2017
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-017-1622-5

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